Cervical cancer, the second most prevalent cancer in women and the fifth cause of death by cancer among women worldwide, is a considerable public health problem. Human papillomavirus (HPV) is the etiologic agent for the vast majority of cervical dysplasia and carcinoma (Dehn et al., 2007). Around 470,000 new cases of cervical cancer are detected annually, mostly in developing nations, of which approximately half of those diagnosed with cervical cancer will die (Beaudenon and Huibregtse, 2008).
Because cervical cancer develops slowly, early detection can lead to a 90-100% cure rate. Papanicolaou smear (Pap smear) screening, a test that only has 50-60% sensitivity, has decreased cervical cancer mortality in the United States and Europe four- to five-fold. Cultural differences and medical infrastructure limitations have limited the successful implementation of Pap smear screening in developing countries.
The intensive medical infrastructure required by and the low sensitivity of the Pap smear test has stimulated searches for other cervical cancer screening techniques. Also, although cervical cytology is a highly effective screening test for cancer, it has limited specificity for clinically significant lesions in cases with low-grade cytologic abnormalities. Up to a quarter of all patients tested may have a false-negative result on the basis of cervical cytology testing alone (Sasagawa, 2009).
Cervical cancer is caused by infection with high-risk HPV, making it a target for screening. HPV testing has been adopted for the triage of patients after a cervical cytology screening test (Pap smear or liquid-based cervical cytology such as ThinPrep or SurePath) interpretation of atypical squamous cells of undetermined significance (ASCUS), and HPV testing is increasingly used for screening in conjunction with cervical cytology (Woodman et al., 2007; Dillner et al., 2008; Saslow et al., 2012). These screening programs are inefficient at identifying individuals at risk for disease, requiring multiple visits over a women's lifetime, which is costly and cumbersome (Brown and Trimble, 2012). Currently, there is a growing interest to switch screening for cervical cancer from Pap smears to more sensitive and cost-effective detection of high-risk HPV. There is also great interest in identifying molecular markers of progression that can identify which patients with high risk HPV and abnormal Pap smears will progress to cervical cancer.
Privacy, cultural and infrastructure issues challenge the effective implementation of cervical cytology and HPV screening for millions of women world-wide. In addition, the projected loss in the Positive Predictive Value (PPV) of cytology in the post vaccination era suggests a need to rely on molecular markers of HPV infection and technologies, such as HPV genotyping, for the new generation of cervical cancer screening, preventive and targeted therapeutics technologies. Furthermore, the United States Food and Drug Administration approval of HPV genotyping tests has led to questions about how typing can assist cervical cancer screening and personalized clinical decisions in a cost-effective manner.